Soluble Receptor for Advanced Glycation End Product Ameliorates Chronic Intermittent Hypoxia Induced Renal Injury, Inflammation, and Apoptosis via P38/JNK Signaling Pathways

• DOI: 10.1155/2016/1015390
• Publication Date: 2016-09-05T21:01:20Z
• Authors: Xu Wu; Wenyu Gu; Huan Lu; Chengying Liu; Biyun Yu; Hui Xu; Yaodong Tang; Shanqun Li; Jian Zhou; Chuan Shao
• Keywords: Advanced glycation end-product; Hypoxia

Obstructive sleep apnea (OSA) associated chronic kidney disease is mainly caused by intermittent hypoxia (CIH) triggered tissue damage. Receptor for advanced glycation end product (RAGE) and its ligand high mobility group box 1 (HMGB1) are expressed on renal cells mediate inflammatory responses in OSA‐related diseases. To determine their roles CIH‐induced injury, soluble RAGE (sRAGE), the neutralizing antibody, was intravenously administered a CIH model. We also evaluated effect of sRAGE inflammation apoptosis. Rats were divided into four groups: (1) normal air (NA), (2) CIH, (3) CIH+sRAGE, (4) NA+sRAGE. Our results showed that accelerated histological injury upregulated RAGE‐HMGB1 levels involving (NF‐ κ B, TNF‐ α , IL‐6), apoptotic (Bcl‐2/Bax), mitogen‐activated protein kinases (phosphorylation P38, ERK, JNK) signal transduction pathways, which abolished but p‐ERK. Furthermore, ameliorated dysfunction attenuating tubular endothelial apoptosis determined immunofluorescence staining CD31 TUNEL. These findings suggested activated cascades contributed to pathogenesis injury. Inhibition interaction provided therapeutic potential inflammation, through P38 JNK pathways.